Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs

Abstract

Necrotizing enterocolitis (NEC) remains the most severe gastrointestinal disorder in preterm infants. It is associated with the initiation of enteral nutrition and may be related to immature carbohydrate digestive capacity. We tested the hypothesis that a formula containing maltodextrin vs. a formula containing lactose as the principal source of carbohydrate would predispose preterm pigs to a higher NEC incidence. Cesarean-derived preterm pigs were given total parenteral nutrition for 48 h followed by total enteral nutrition with a lactose-based (n = 11) or maltodextrin-based (n = 11) formula for 36 h. A higher incidence (91% vs. 27%) and severity (score of 3.3 vs. 1.8) of NEC were observed in the maltodextrin than in the lactose group. This higher incidence of NEC in the maltodextrin group was associated with significantly lower activities of lactase, maltase, and aminopeptidase; reduced villus height; transiently reduced in vivo aldohexose uptake; and reduced ex vivo aldohexose uptake capacity in the middle region of the small intestine. Bacterial diversity was low for both diets, but alterations in bacterial composition and luminal concentrations of short-chain fatty acids were observed in the maltodextrin group. In a second study, we quantified net portal absorption of aldohexoses (glucose and galactose) during acute jejunal infusion of a maltodextrin- or a lactose-based formula (n = 8) into preterm pigs. We found lower net portal aldohexose absorption (4% vs. 42%) and greater intestinal recovery of undigested carbohydrate (68% vs. 27%) in pigs acutely perfused with the maltodextrin-based formula than those perfused with the lactose-based formula. The higher digestibility of the lactose than the maltodextrin in the formulas can be attributed to a 5- to 20-fold higher hydrolytic activity of tissue-specific lactase than maltases. We conclude that carbohydrate maldigestion is sufficient to increase the incidence and severity of NEC in preterm pigs.

Physical activity level is impaired and diet dependent in preterm newborn pigs

“…associated with increases in key functions such as digestive enzyme activity, nutrient absorption, and immunological tolerance to bacterial colonization (27,(33)(34)(35). Our follow-up studies show that the difference in intestinal mass per body weight between preterm and term pigs on day 5 disappears over the following weeks but that the general deficits in body growth and many behavioral characteristics (regardless of diet during the first 5 d) remain until at least 4 wk of age (36).…”

“…Colostrum contains high concentrations of trophic and immunoregulatory factors (24) and a rapid progression of enteral feeding with BC or porcine colostrum (120 ml/ kg/d from day 3 after birth) results in less NEC in preterm pigs, relative to IF (25,26). It is noteworthy in this study that IF remained inferior to BC and HM, even using a relatively slow (27). Furthermore, IF products are clearly inferior to intact milk products in stimulating immunity and mucosal defense mechanisms (28)(29)(30).…”

Deregulation of intestinal anti-microbial defense by the dietary additive, maltodextrin

“…16 Additionally, MDX consumption by preterm piglets lead to the expansion of ileal E. coli populations 17 and induced necrotizing enterocolitis in these animals, but not in fully developed pigs. 18 Increased levels of E. coli and AIEC strains have been repeatedly observed in ileal CD patients, suggesting a role for E. coli in disease pathogenesis. [19][20][21] In earlier work from our laboratory, we found that patients with ileal CD have a mucosal microbiome enriched for MDX metabolism, as compared to colonic CD patients and non-IBD controls.…”

“…Notable studies have demonstrated a direct effect of these compounds on mucosal barrier integrity, which translates to exacerbated intestinal inflammation or increased bacterial burdens in animal models. 17,18,27 Likewise, restrictive diets that eliminate processed foods are showing clinical Figure 3. Consumption of MDX decreases the mucosal barrier of the intestine and increases the proximity of commensal bacteria to the epithelial layer.…”

Nutrient-intake-level-dependent regulation of intestinal development in newborn intrauterine growth-restricted piglets via glucagon-like peptide-2

“…This inconsistency might be related to the digestibility of nutrients for the premature pig. It has been reported that the less-digestible maltodextrin-based formula induced higher incidences of necrotizing enterocolitis compared with the highly digestible lactose-based formula in preterm pigs (Thymann et al, 2009). This raises the question of how the composition of the formula could impact the intestinal development of IUGR neonates.…”